Tsis ntev los no, British Journal of Clinical Pharmacology tau tshaj tawm thawj cov lus qhia kho mob uas tau tsim los ntawm UK Center of Excellence for Regulatory Science and Innovation in Pharmacogenomics (CERSI PGx), hu ua "CYP2C19 genotype testing for clopidogrel: Ib cov lus qhia uas tau tsim los ntawm UK Center of Excellence for regulatory science and innovation in pharmacogenomics (CERSI PGx)". Daim ntawv tseem ceeb no tsom mus rau qhov tseem ceeb ntawm kev kho mob ntawm CYP2C19 genotyping hauv kev taw qhia kev kho mob clopidogrel.
Txog CERSI PGx
CERSI PGx yog ib qho ntawm xya lub chaw tshawb fawb txog kev cai lij choj thiab kev tsim kho tshiab uas tsoomfwv UK txhawb nqa uas tau tsim tsa thaum Lub Ib Hlis 2025. Ua tus thawj coj ntawm University of Liverpool, nws tau txais nyiaj los ntawm Innovate UK, Medical Research Council (MRC), Medicines and Healthcare products Regulatory Agency (MHRA), thiab Office for Life Sciences (OLS). Lub chaw no lub hom phiaj yog kom ua kom muaj kev sib koom ua ke ntawm pharmacogenomics (PGx) rau hauv National Health Service (NHS) kom muaj kev nyab xeeb thiab ua tau zoo los ntawm kev daws teeb meem tseem ceeb ntawm kev siv. Cov lus qhia no yog thawj cov lus qhia kho mob txij li thaum CERSI PGx tau tsim.
Vim li cas CYP2C19 thiaj tseem ceeb rau Clopidogrel
CYP2C19 yog ib tug tswv cuab tseem ceeb ntawm tsev neeg cytochrome P450 enzyme, uas yog lub luag haujlwm rau kev ua haujlwm ntawm ntau yam tshuaj hauv lub cev. Cov kev hloov pauv ntawm cov noob caj noob ces hauv CYP2C19 ua rau muaj qhov sib txawv ntawm cov tshuaj hauv lub cev, uas cuam tshuam rau kev ua haujlwm zoo thiab kev nyab xeeb.
Clopidogrel yog ib yam tshuaj uas siv dav dav los tiv thaiv cov teeb meem thrombotic hauv cov kab mob coronary artery, ischaemic stroke, peripheral artery disease, thiab atrial fibrillation. Ua ib qho prodrug, clopidogrel xav tau kev ua haujlwm metabolic los ntawm CYP2C19. Cov lus qhia faib cov tib neeg ua ultrarapid, rapid, normal, intermediate, thiab poor metabolilisers raws li CYP2C19 genotype. Cov neeg nqa cov alleles ntawm kev poob haujlwm (piv txwv li, CYP2C192 thiab *3*) - intermediate thiab poor metabolilisers - tsis tuaj yeem ua haujlwm clopidogrel zoo, ua rau platelet inhibition tsis txaus thiab muaj kev pheej hmoo ntawm kev rov qab thrombosis.
Qhov zaus ntawm CYP2C192 allele yog kwv yees li 15% hauv cov neeg European, 30% hauv cov neeg Esxias Qab Teb, thiab siab txog 60% hauv cov pej xeem Oceanian hauv paus txawm.
Cov Lus Qhia Tseem Ceeb: Kev Ntsuas CYP2C19 Rau Clopidogrel
Cov lus qhia hais tias, txawm tias qhov qhia txog dab tsi los xij, txhua tus neeg mob uas xav txog clopidogrel yuav tsum tau mus dhau qhov kev xeem.CYP2C19kev tshuaj ntsuam genotyping.Raws li cov txiaj ntsig, kev kho mob antiplatelet yuav tsum tau ua kom zoo dua:
-Cov metabolism tsis zooyuav tsum tsis txhob siv clopidogrel thiab siv lwm yam tshuaj uas tsis vam khom CYP2C19 metabolism, xws li ticagrelor lossis prasugrel.
-Cov tshuaj metabolizer nruab nrabyuav tsum xav txog lwm cov tshuaj lossis cov txheej txheem kho dua tshiab es tsis txhob tsuas yog nce cov koob tshuaj clopidogrel xwb.
Hauv UK, clopidogrel tau pom zoo rau kev tiv thaiv theem ob ntawm cov xwm txheej atherothrombotic, rau qhov nruab nrab mus rau qhov muaj feem yuav mob transient ischaemic attack (TIA) lossis mob stroke me me, thiab rau kev tiv thaiv cov xwm txheej atherothrombotic thiab thromboembolic hauv atrial fibrillation.
Dhau ntawm Clopidogrel: Lwm Cov Tshuaj Uas CYP2C19 Genotyping Yog Qhov Tseem Ceeb
Tus nqi ntawm CYP2C19 genotyping nthuav dav mus deb tshaj clopidogrel. Ua ib qho enzyme metabolising tshuaj loj, CYP2C19 kuj ua lub luag haujlwm tseem ceeb hauv kev metabolism ntawm voriconazole, ntau yam antidepressants, thiab proton twj inhibitors (PPIs). Ntau lub tebchaws thiab lub tebchaws cov lus qhia pom zoo genotype coj tus kheej rau cov tshuaj no.
1. Cov Tshuaj Tiv Thaiv Kev Nyuaj Siab (SSRIs)
Cov tshuaj xaiv serotonin reuptake inhibitors (SSRIs) - xws li sertraline, citalopram, thiab escitalopram - yog cov tshuaj kho mob thawj zaug rau kev nyuaj siab thiab feem ntau yog metabolised los ntawm CYP2C19. CYP2C19 enzyme kev ua haujlwm ncaj qha txiav txim siab qhov plasma concentration ntawm cov tshuaj no. Cov metabolizers tsis zoo muaj 30%–60% txo qis hauv kev tshem tawm cov tshuaj, uas ua rau lawv muaj cov teebmeem tsis zoo xws li QT interval ntev thiab sedation. Ultrarapid metabolizers feem ntau muaj cov plasma concentration subtherapeutic, ua rau kev kho mob qeeb thiab muaj kev pheej hmoo ntawm kev tso tseg tshuaj.
Xyoo 2023 Clinical Pharmacogenetics Implementation Consortium (CPIC) cov lus qhia hais tias cov neeg uas tsis muaj zog metabolizers noj citalopram lossis escitalopram muaj feem yuav QT ntev dua thiab pom zoo kom txo cov tshuaj kom tsawg li 50%. Xyoo 2021 Dutch Pharmacogenetics Working Group (DPWG) cov lus qhia qhia tias cov neeg uas tsis muaj zog metabolizers yuav tsum tau txais cov tshuaj escitalopram ntau tshaj plaws kom txo tau 50%, thiab cov neeg uas siv ultrarapid metabolizers yuav tsum tsis txhob siv escitalopram kiag li. Rau sertraline, DPWG pom zoo kom noj tshuaj txhua hnub tsis pub tshaj 75 mg rau cov neeg uas tsis muaj zog metabolizers.
Qhov tseem ceeb, tsab ntawv xov xwm Chinese Expert Consensus on Pharmacogenomic Testing in Psychiatry (2025) uas nyuam qhuav luam tawm - tsim los ntawm Precision Medicine Collaboration Group ntawm Chinese Society of Psychiatry - muaj cov lus qhia rau CYP2C19 genotyping. Cov lus pom zoo sau tseg tias cov lus qhia txog kev hloov kho koob tshuaj los ntawm cov lus qhia thoob ntiaj teb xws li CPIC thiab DPWG rau cov tshuaj enzymes metabolising (suav nrog CYP2C19) tuaj yeem siv rau cov pej xeem Suav. Yog li ntawd, CYP2C19 genotyping ua ntej pib kho SSRI (piv txwv li, escitalopram) ua rau muaj kev kho kom zoo dua lossis hloov mus rau lwm cov tshuaj uas tsis metabolised los ntawm CYP2C19, yog li ua tiav kev kho mob raug, txhim kho cov nqi teb, thiab txo cov xwm txheej tsis zoo.
2. Cov Tshuaj Proton Pump Inhibitors (PPIs)
Cov tshuaj proton pump inhibitors – suav nrog omeprazole, lansoprazole, thiab pantoprazole – yog siv dav rau cov kab mob acid xws li kab mob gastroesophageal reflux thiab peptic ulcers. Lawv cov metabolism kuj nyob ntawm CYP2C19 heev. Cov neeg mob uas muaj CYP2C19 genotypes sib txawv qhia txog kev hloov pauv tseem ceeb hauv kev teb rau PPIs. Cov neeg nqa cov alleles poob haujlwm (*2, *3) tau nce kev siv tshuaj ntau ntxiv, uas yuav ua rau kom muaj kev tswj cov kua qaub ntau ntxiv tab sis kuj ua rau muaj kev pheej hmoo ntawm cov teeb meem tsis zoo. Qhov sib txawv, cov metabolizers ib txwm muaj cov plasma concentration qis dua thiab yuav muaj kev tswj cov kua qaub tsawg dua, txawm hais tias kev hloov pauv ntawm tus kheej tseem ceeb heev.
Xyoo 2020 CPIC cov lus qhia rau PPIs qhia tias cov tshuaj metabolizers uas siv omeprazole lossis cov tshuaj zoo sib xws yuav metabolize cov tshuaj sai dhau, ua rau cov plasma concentration tsis txaus thiab tsis muaj acid suppression zoo. Hauv cov neeg mob no, yuav tsum tau nce cov koob tshuaj thiab saib xyuas kev teb kho mob. Rau cov metabolizers uas tsis zoo, kev tshem tawm cov tshuaj qeeb thiab cov plasma concentration yuav nce siab; thaum qhov ua tau zoo dua, qhov muaj peev xwm ua rau muaj tshuaj lom ntau ntxiv. Kev txo cov koob tshuaj thiab kev saib xyuas kev teb yog qhov tsim nyog. Yog li ntawd, rau cov neeg mob uas pib kho PPI lossis cov neeg uas muaj kev teb tsis zoo lossis cov teebmeem tsis zoo, kev kuaj CYP2C19 genotyping raug pom zoo kom coj kev noj tshuaj rau tus kheej, ua kom zoo dua, thiab txo cov teebmeem tsis zoo.
3. Voriconazole
Voriconazole yog ib hom tshuaj tua kab mob uas siv dav dav los kho cov kab mob fungal loj xws li aspergillosis uas nkag mus rau hauv lub cev. Nws muaj lub sijhawm kho mob nqaim: cov ntshav siab dhau heev ua rau muaj kev pheej hmoo ntawm kev ua rau lub siab puas tsuaj thiab kev cuam tshuam rau qhov muag, thaum cov ntshav qis ua rau kev kho mob tsis ua haujlwm. Kev ua haujlwm ntawm voriconazole feem ntau yog los ntawm CYP2C19, thiab cov kev hloov pauv ntawm cov noob caj noob ces muaj kev cuam tshuam loj heev rau nws cov ntshav.
Xyoo 2016, CPIC tau tshaj tawm cov lus qhia tshwj xeeb txog CYP2C19 thiab voriconazole. Nws hais tias cov tshuaj metabolizers uas siv ceev heev tau txo cov tshuaj voriconazole trough concentration thiab feem ntau tsis ua tiav cov theem kho mob uas xav tau. Cov tshuaj metabolizers uas siv ceev heev tau nce cov concentration trough concentration thiab muaj kev pheej hmoo ntau ntxiv ntawm cov kev tsis zoo. Cov lus qhia ntawm CPIC muab cov lus qhia txog kev siv tshuaj raws li genotype. Piv txwv li, cov neeg laus uas siv ceev heev yuav tsum tau txais lwm cov tshuaj uas tsis nyob ntawm CYP2C19 metabolism, xws li isavuconazole, liposomal amphotericin B, lossis posaconazole. Yog li ntawd, CYP2C19 genotyping ua ntej kev kho mob voriconazole ua rau muaj kev siv tshuaj raws li tus kheej thiab txo qhov tshwm sim ntawm cov xwm txheej tsis zoo ntsig txog tshuaj.
Qhov Tseem Ceeb Hauv Kev Kho Mob: Ua Rau Kev Siv Tshuaj Txhim Kho Dua
Cov lus qhia tshiab uas tau tso tawm dua ib zaug ntxiv tso CYP2C19 genotyping rau pem hauv ntej ntawm kev kho mob kom raug. Txawm li cas los xij, nws yog ib qho tseem ceeb kom paub tias cov kev siv kho mob ntawm CYP2C19 genotyping mus deb tshaj li clopidogrel - los ntawm voriconazole (tshuaj tua kab mob fungal) thiab SSRIs (tshuaj tiv thaiv kev nyuaj siab) mus rau cov tshuaj proton twj tso kua qaub rau kev tswj cov kua qaub. CYP2C19 genotype ua haujlwm ua "lub koob qhia" rau kev kho mob tshuaj.
Thaum kev kho mob precision tau txais kev lees paub dav dua, ntau cov lus qhia tseem ceeb tau suav nrog CYP2C19 genotyping rau hauv cov txheej txheem kho mob niaj hnub. Rau cov neeg mob, kev paub lawv tus kheej CYP2C19 genotype pab lawv nkag siab txog lawv cov lus teb rau tshuaj thiab ua rau muaj kev txiav txim siab sib koom nrog lawv tus kws kho mob los tsim txoj kev npaj kho mob zoo dua. Rau cov kws kho mob, kev koom ua ke cov txiaj ntsig ntawm kev kuaj mob genetic rau hauv kev txiav txim siab sau ntawv yog ib txoj hauv kev muaj zog los txhim kho qhov zoo ntawm kev kho mob thiab xyuas kom meej tias tus neeg mob muaj kev nyab xeeb.
Kev Ntsuas Macro & Micro'sKev daws teeb meem CYP2C19 genotyping
Macro & Micro Test muaj cov khoom siv CYP2C19 genotyping raws li kev txhim kho amplification refractory mutation system (ARMS) ua ke nrog Taqman probes nrog cov yam ntxwv hauv qab no:
-Kev them nqi allele tag nrho- ntes tauCYP2C192, *3, thiab *17tsis muaj qhov ploj ntawm cov variants tseem ceeb.
-Kev tswj xyuas zoo- suav nrog cov kev tswj tsis zoo/zoo, kev tswj sab hauv, thiab UDG enzyme rau plaub theem kev tswj zoo kom ntseeg tau tias muaj txiaj ntsig zoo.
-Kev rho tawm tsis siv neeg- sib xws nrog Macro & Micro-Test lub tshuab rho tawm nucleic acid uas ua haujlwm tau tag nrho, txhim kho kev ua haujlwm kom zoo.
-Kev sib raug zoo dav dav- ua haujlwm nrog cov cuab yeej PCR tiag tiag hauv khw, suav nrog ABI 7500 Hongshi SLAN 96P.
-Kev txhais lus tshwm sim tsis siv neeg– software tsom xam tshwj xeeb (ntawm ABI 7500, SLAN 96P, thiab lwm yam) ua rau muaj peev xwm txhais cov txiaj ntsig tau yam tsis tas siv neeg, ua kom muaj txiaj ntsig zoo dua.
-POCT npaj txhij rau kev siv tshuab– HWTS AIO800 Lub Tshuab Ntsuas Nucleic Acid Amplification Ua Haujlwm Tag Nrho Ua Rau "sample in, result out".
Nrog rau kev nce qib tas mus li ntawm pharmacogenomics, CYP2C19 genotyping yuav pab tau ntau tus neeg mob, hloov kev kho mob kom raug los ntawm lub tswv yim mus rau kev kho mob niaj hnub. Cov lus qhia CERSI PGx tshiab tshaj tawm txhawb nqa lub luag haujlwm tseem ceeb ntawm CYP2C19 kev kuaj tsis yog rau clopidogrel xwb tab sis kuj rau cov npe tshuaj uas loj hlob tuaj, suav nrog cov tshuaj antidepressants, cov tshuaj proton twj tso kua mis inhibitors, thiab voriconazole. Txhawm rau pab txhawb kev siv dav dav ntawm kev sau ntawv genotype, kev daws teeb meem kev kuaj mob txhim khu kev qha thiab yooj yim rau cov neeg siv yog qhov tseem ceeb. Macro & Micro-Test's pharmacogenomic kev kuaj mob portfolio, uas muaj kev npog allele tag nrho, kev tswj hwm zoo, thiab cov platforms npaj txhij rau automation, lub hom phiaj yog txhawb nqa cov kws kho mob hauv kev siv tshuaj kom raug thiab thaum kawg tiv thaiv kev noj qab haus huv ntawm tus neeg mob.
Cov Khoom Sib Xws:
Cov ntaub ntawv siv los ua piv txwv:
1.Lima JJ, Thomas CD, Barbarino J, thiab lwm tus. Cov Lus Qhia Txog Kev Siv Clinical Pharmacogenetics Implementation Consortium (CPIC) rau CYP2C19 thiab Proton Pump Inhibitor Dosing. Clin Pharmacol Ther. 2020. doi:10.1002/cpt.20151.
2. Lee CR, Luzum JA, Sangkuhl K, thiab lwm tus. Cov Lus Qhia Txog Kev Siv Tshuaj Kho Mob Hauv Tsev Kho Mob rau CYP2C19 Genotype thiab Clopidogrel Therapy: 2022 Hloov Tshiab. Clin Pharmacol Ther. 2022. doi:10.1002/cpt.25261.
3. Lub Koom Haum Hauv Tebchaws rau Kev Noj Qab Haus Huv thiab Kev Saib Xyuas Zoo Tshaj Plaws (NICE). Kev kuaj mob CYP2C19 genotype los qhia kev siv clopidogrel tom qab mob stroke ischaemic lossis transient ischaemic attack. Kev taw qhia kev kuaj mob DG59. Luam tawm: 31 Lub Xya Hli 2024.
4.Precision Medicine Research Collaboration Group ntawm Suav Society of Psychiatry. Kev pom zoo ntawm cov kws tshaj lij txog kev sim tshuaj pharmacogenomic hauv kev puas siab puas ntsws (2025) [Zhonghua Jing Shen Ke Za Zhi].Phau Ntawv Xov Xwm Txog Kev Kho Mob Hlwb Hauv Suav Teb. 2025;58(6):434-445. doi:10.3760/cma.j.cn11366120240611-00181
5.Dello Russo C, Frater I, Kuruvilla R, et al. Kev kuaj CYP2C19 genotype rau clopidogrel: Ib qho lus qhia tsim los ntawm UK Center of Excellence rau kev tswj hwm kev tshawb fawb thiab kev tsim kho tshiab hauv pharmacogenomics (CERSI-PGx). Br J Clin Pharmacol. 2025. DOI: 10.1093/bjcp/…
6. Moriyama B, Owusu Obeng A, Barbarino J, thiab lwm tus. Cov Lus Qhia Txog Kev Siv Tshuaj Kho Mob Hauv Tsev Kho Mob (CPIC) rau CYP2C19 thiab Voriconazole Therapy. Clin Pharmacol Ther. 2017;102(1):45-51. doi:10.1002/cpt.595.
7. Bousman CA, Stevenson JM, Ramsey LB, thiab lwm tus. Cov Lus Qhia Txog Kev Siv Tshuaj Kho Mob Hauv Tsev Kho Mob (CPIC) rau CYP2D6, CYP2C19, CYP2B6, SLC6A4, thiab HTR2A Genotypes thiab Serotonin Reuptake Inhibitor Antidepressants. Clin Pharmacol Ther. 2023;114(1):51-68. doi:10.1002/cpt.2903.
8.Brouwer JMJL, Nijenhuis M, Soree B, thiab lwm tus. Dutch Pharmacogenetics Working Group (DPWG) cov lus qhia rau kev sib cuam tshuam ntawm cov noob caj noob ces thiab tshuaj ntawm CYP2C19 thiab CYP2D6 thiab SSRIs. Eur J Hum Genet. 2021. doi:10.1038/s41431-021-00894-2.
Lub sijhawm tshaj tawm: Plaub Hlis-22-2026